Fixed-Dose Enoxaparin Prophylaxis Is Inadequate for the Majority of Surgical Patients and Inadequate Dosing Predicts Postoperative Venous Thromboembolism

Pannucci, Christopher J.; Jones, Daniel L.; Bertolaccini, Corinne; Fleming, Kory I.; Wall, Vanessa; Stringham, James C.; Cochran, Amalia; Pickron, Bartley; Varghese, Tom; Prazak, Ann Marie

doi:10.1016/j.jvsv.2017.12.031

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“…We found that weight-based enoxaparin (0.5 mg/kg twice daily) was not inferior to fixed-dose enoxaparin (40 mg twice daily) for avoidance of underanticoagulation, and that weight-based enoxaparin was superior to fixed-dose enoxaparin for avoidance of overanticoagulation. FIVE trial data have relevance beyond pharmacokinetic optimization, because studies in plastic surgery, 16 orthopedic surgery, 25,33 trauma surgery, 19,20,29 and surgical patients in general 34 have shown that inadequate anticoagulation significantly increases postoperative venous thromboembolism risk, and studies in orthopedic surgery have correlated high anti-factor Xa levels with increased risk for bleeding. 25 Our data are consistent with prior nonrandomized studies suggesting that weight-based enoxaparin dosing is pharmacokinetically superior to fixed-dose enoxaparin in surgical patients.…”

Section: Discussionmentioning

confidence: 99%

“…19 Our group's aggregate data from 577 surgical patients receiving twice-daily enoxaparin clearly show a significant increased risk for 90-day symptomatic venous thromboembolism in patients with low versus adequate peak anti-factor Xa levels (6.2 percent versus 1.5 percent; p = 0.003). 17,33,34,43 Whether these data are generalizable to all surgical patients is unknown. Arguably, the plastic and reconstructive surgery population is the ideal population on which to test concepts for surgical patients in general, as plastic surgery inpatients represent a cross-section of surgical patients.…”

Section: Limitationsmentioning

confidence: 99%

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Optimal Dosing of Prophylactic Enoxaparin after Surgical Procedures: Results of the Double-Blind, Randomized, Controlled FIxed or Variable Enoxaparin (FIVE) Trial

Pannucci

Fleming

Bertolaccini³

et al. 2021

Plastic &Amp; Reconstructive Surgery

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Background:The accepted "one-size-fits-all" dose strategy for prophylactic enoxaparin may not optimize the medication's risks and benefits after surgical procedures. The authors hypothesized that weight-based administration might improve the pharmacokinetics of prophylactic enoxaparin when compared to fixed-dose administration. Methods: The FIxed or Variable Enoxaparin (FIVE) trial was a randomized, doubleblind trial that compared the pharmacokinetic and clinical outcomes of patients assigned randomly to postoperative venous thromboembolism prophylaxis using enoxaparin 40 mg twice daily or enoxaparin 0.5 mg/kg twice daily. Patients were randomized after surgery and received the first enoxaparin dose at 8 hours after surgery. Primary hypotheses were (1) weight-based administration is noninferior to a fixed dose for avoiding underanticoagulation (anti-factor Xa <0.2 IU/ml) and (2) weight-based administration is superior to fixed-dose administration for avoiding overanticoagulation (anti-factor Xa >0.4 IU/ml). Secondary endpoints were 90-day venous thromboembolism and bleeding. Results: In total, 295 patients were randomized, with 151 assigned to fixed-dose and 144 to weight-based administration of enoxaparin. For avoidance of underanticoagulation, weight-based administration had a greater effectiveness (79.9 percent versus 76.6 percent); the 3.3 percent (95 percent CI, -7.5 to 12.5 percent) greater effectiveness achieved statistically significant noninferiority relative to the a priori specified −12 percent noninferiority margin (p = 0.004). For avoidance of overanticoagulation, weight-based enoxaparin administration was superior to fixed-dose administration (90.6 percent versus 82.2 percent); the 8.4 percent (95 percent CI, 0.1 to 16.6 percent) greater effectiveness showed significant safety superiority (p = 0.046). Ninety-day venous thromboembolism and major bleeding were not different between fixed-dose and weight-based cohorts (0.66 percent versus 0.69 percent, p = 0.98; 3.3 percent versus 4.2 percent, p = 0.72, respectively). Conclusion: Weight-based administration showed superior pharmacokinetics for avoidance of underanticoagulation and overanticoagulation in postoperative patients receiving prophylactic enoxaparin.

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